Abstract

Enterovirus infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic
islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic
factor. This study evaluates whether gut mucosa is a reservoir for enterovirus persistence in type 1 diabetic patients. Small-bowel
mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed
for the presence of enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus
was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA
deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with
a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting
defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation.
The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent enterovirus infection associated
with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1
diabetes.